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PLoS One. 2014 Mar 19;9(3):e91597. doi: 10.1371/journal.pone.0091597. eCollection 2014.

Endotoxin-induced monocytic microparticles have contrasting effects on endothelial inflammatory responses.

Author information

1
Vascular Immunology Unit, Sydney Medical School & Bosch Institute, University of Sydney, Camperdown, Australia.
2
Weill Medical College, Cornell University, New York, New York, United States of America.
3
Institut Cochin, INSERM U1016, Paris, France; CNRS, UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Abstract

Septic shock is a severe disease state characterised by the body's life threatening response to infection. Complex interactions between endothelial cells and circulating monocytes are responsible for microvasculature dysfunction contributing to the pathogenesis of this syndrome. Here, we intended to determine whether microparticles derived from activated monocytes contribute towards inflammatory processes and notably vascular permeability. We found that endotoxin stimulation of human monocytes enhances the release of microparticles of varying phenotypes and mRNA contents. Elevated numbers of LPS-induced monocytic microparticles (mMP) expressed CD54 and contained higher levels of transcripts for pro-inflammatory cytokines such as TNF, IL-6 and IL-8. Using a prothrombin time assay, a greater reduction in plasma coagulation time was observed with LPS-induced mMP than with non-stimulated mMP. Co-incubation of mMP with the human brain endothelial cell line hCMEC/D3 triggered their time-dependent uptake and significantly enhanced endothelial microparticle release. Unexpectedly, mMP also modified signalling pathways by diminishing pSrc (tyr416) expression and promoted endothelial monolayer tightness, as demonstrated by endothelial impedance and permeability assays. Altogether, these data strongly suggest that LPS-induced mMP have contrasting effects on the intercellular communication network and display a dual potential: enhanced pro-inflammatory and procoagulant properties, together with protective function of the endothelium.

PMID:
24646764
PMCID:
PMC3960107
DOI:
10.1371/journal.pone.0091597
[Indexed for MEDLINE]
Free PMC Article

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